In the United States, spironolactone is the oral anti-androgen of choice for trans women. It’s the cheapest and is well tolerated by most people. Outside of the United States cyproterone acetate, also known as Androcur, is the preferred drug. This week I take a look at this drug, how it works, and why it hasn’t been approved for use in the United States.

The chemical structure of cyproterone

Cyproterone is an anti-androgen. It blocks androgen receptors, preventing testosterone and other androgens from having their effects. By blocking those receptors, it reduces the amount of testosterone in the body through a mechanism called negative feedback. Cyproterone is chemically similar to progesterone and has some progesterone-like effects as well. Outside of transgender care it’s also used for prostate cancer, as combination antiandrogen and hormonal birth control for cis women (e.g., Dianette), and for chemical castration of sex offenders.

It’s available both as a pill and intramuscular injection. The pill form should be taken every day at the same time after a meal. The dose often used for transition in the literature is 100mg/day. Anecdotally I’ve been told that lower doses, such as 25-50mg/day, have been used. The injection is given once every 1-2 weeks.

Cyproterone acetate is not risk-free and is definitely not for everyone. Most seriously, cyproterone is associated with liver damage. That damage can be severe. It can lead to liver failure even after the drug is stopped. Damage has been reported with doses over 100mg/day. Because of this, people on cyproterone should have their livers regularly monitored with blood tests. The drug should not be combined with other drugs that can cause liver damage. That includes alcohol and many prescription drugs. Individuals with known liver damage/disease should not take cyproterone.

There is also some question of whether the drug is associated with some cancers. In particular, liver cancer and some brain cancers. Specifically, hepatocellular carcinoma and meningioma are the cancers of concern. Researchers are still exploring this connection. Other negative side effects of cyproterone include allergic reactions and worsening of depression.

Many trans women are concerned about fertility. The effects of cyproterone alone, without estrogen, on fertility are somewhat known. Sperm count goes down with oral doses as low as 50mg. Infertility can happen in as little as 2 months. The infertility is reversible once cyproterone is stopped. Fertility returns anywhere from 3-20 months. But remember — no anti-androgen is a birth control method. Please use birth control if you or your partner are at risk of pregnancy.

In the literature, 100mg/day is the dose that seems to be preferred for transition. No cases of liver cancer in trans women have been reported. However some women do have higher levels of liver enzymes. That’s a sign that the drug is causing some damage to liver cells. Transdermal, instead of oral, estrogen is recommended to reduce potential liver damage and blood clots.

Cyproterone is a potential alternative for trans women. So why hasn’t the FDA approved it? That’s a little murky. I wasn’t able to find public document describing the reasoning. But the biggest reason cited by other sources is the concern of liver damage. The FDA is likely trying to do its job and protect the population from drugs that cause more harm than good. In its efforts it may well overstretch. Cyproterone only rarely causes liver problems, and those problems can be screened for with regular blood tests. However it’s important to remember that there are safer alternatives still available. Spironolactone and the GnRH agonists (puberty blockers) are generally safer and mostly well tolerated. Other androgen receptor blockers (e.g., bicalutamide), while not in common use for trans care, are also available and have lower rates of liver damage. So there’s little pressure on the FDA to approve a riskier drug.

So in summary — cyproterone is an androgen receptor blocker in use outside the United States for trans care, prostate cancer, and birth control. It’s biggest side effect is potential liver damage. It’s not FDA-approved for use in the US probably because of that liver damage. People currently using the drug should be under a physician’s supervision.

Note on references — I pulled most of my information from LexiComp, which I have access to through my university and can’t easily reference. However, prescribing information is publicly available and has much of the same information.

The science of transgender is still in its infancy, but evidence so far points to it being biological. Differences in brain have been seen, and I’ve covered them before here on OMH. However, genetic evidence is also being published! This week, let’s take a look at CYP17. CYP17 is a gene that makes enzymes that are part of sex hormone synthesis. Mutations in CYP17 have been noted in some intersex conditions, such as adrenal hyperplasia.

Now, there’s a SNP that’s been noticed in CYP17. SNPs are “single nucleotide polymorphisms”, which takes some explaining. SNPs are very, very tiny mutations in genes — just one letter in the DNA alphabet changes! SNPs don’t usually change the protein that the gene makes very much.

So we have this gene — CYP17, that is involved in making sex hormones. And we have this tiny mutation, this SNP. Now let’s look at the science!

Specifically, let’s look at this one study that was published back in 2008. They looked at the CYP17 gene in 102 trans women, 49 trans men, 756 cis men, and 915 cis women. They compared the CYP17 of trans women to cis men, and trans men to cis women. Unlike many studies, this comparison makes sense. We’re talking about the DNA in the genes here, not something that’s changed by hormonal status.

They found multiple things:

There was no difference between trans women and cis men

Trans men were more likely to have a SNP in their CYP17 than cis women were.

Cis men, trans women, and trans men all had the SNP more frequently than cis women

What does that mean?

We don’t know yet. But it does appear that CYP17 is a gene that it might be worth looking deeper into to find potential causes for transgender.

Recent reports have highlighted the frequency of non-suicidal self-injury among gender and sexual minorities. 41.9% of transgender people have self-injured. I was unable to find a percentage for cis lesbian, gay and bisexual people beyond the general report that the rate was “much higher”. Gender and sexual minority (GSM) youth are at particular risk, as are cis women.

So let’s take a quick look at non-suicidal self injury this week. What is it? Why do people do it? And what should those who currently self-injure, and their loved ones, know?

Non-suicidal self injury (NSSI) is a term that refers to deliberate attempts to cause oneself injury without intending suicide. The “without intending suicide” is the important bit there. This is a separate phenomenon from suicidality, though both suicidality and NSSI can come from the same psychological source. NSSI can take many forms, but cutting and burning are the most common. People who have higher levels of stress, such as GSMs, are at higher risk for NSSI. Transgender people may have an additional risk factor because of extreme body dysphoria.

To most who have never participated in NSSI, it can seem baffling. Why would a person do that to themselves? While everyone has different reasons, at core NSSI is about survival. Many use it to defuse overwhelming emotions. Emotional pain is just like physical pain in the brain, causing activation of the same areas. All pain causes the release of morphine-like chemicals in the brain which buffer the pain, causing the sensation of a “high”. By creating physical pain in reaction to emotional pain, the person doing the NSSI can regulate their own emotions and cope. Other people who do NSSI are attempting to focus. When the world seems far away or they feel numb, pain can help them to feel something and give something to concentrate on. Lastly, some people who do NSSI do so as a way to punish themselves, as a way of asserting control in a powerless situation, or to communicate their emotional pain….or for any number of other highly personal reasons.

NSSI is not an ideal way of coping with life’s stressors. It can be addictive. It’s easy to hurt oneself too much and accidentally attempt suicide or develop infection. Scars and NSSI behavior attract attention, limiting one’s ability to get or maintain a job. Over time it can permanently change a person’s responses to stress and pain.

NSSI is often misunderstood, even in psychology and medicine. Most psychologists and physicians have never experienced NSSI or been close to people who have, so they fail to understand the reasons for NSSI. Until the DSM-V, the only psychological diagnosis that applied was that of borderline personality disorder, which most people who do NSSI do not have.

It can be difficult for a person who self harms to get help. Psychologists and physicians are legally bound to report individuals who are at risk of harming themselves or others to the police. While necessary, it limits confidentiality and can harm trust. Some professionals require that a patient sign a “no self harm contract” before receiving any treatment. Not all patients are willing or able to sign such a contract. Physicians have a limited set of options for treatment: medications (which can take 4-6 weeks to begin to work), referral to a psychologist or psychiatrist, do some level of psychological intervention themselves, or admit the patient to the hospital. And then there’s the question of affordability, especially if you’re unable to hold a job because of the self injury.

Despite these barriers, psychological and medical professionals can be very helpful for people seeking to stop self-injuring. At bare minimum, having a psychologist or physician in the loop can help if a particular incident of self injury goes further than intended. NSSI is a coping strategy, and psychologists and physicians can be very helpful for the issues lying underneath self injury, whether that’s depression, post traumatic stress disorder, or just plain stress.

Lastly, it’s important to know that people can and do learn non-NSSI coping strategies and learn to be self-injury free.

If you want to learn more about non-suicidal self injury, I highly recommend this website. It’s old and the current version is broken, so that links off to the Wayback machine version. It’s still one of the best sites written by people who intimately understand self injury and work to provide information and help others. For a modern alternative, this website also has support forums.

Have you heard that some herbs and foods contain chemicals called “phytoestrogens” that work like estrogen in the body? Ever seen products being sold over the counter advertised to “feminize naturally” or “prevent hot flashes during menopause”? Or read conversations online about using over the counter products to feminize instead of prescribed hormones? Did you stop and wonder if there was truth to the claims? Let’s do a quick overview and do some debunking!

What are phytoestrogens?

Phytoestrogens are estrogen-like chemicals made by plants. Just like how the tobacco plant makes nicotine to defend itself against insects, phytoestrogens are thought to have a protective effect for the plant. One of the most commonly known phytoestrogen is soy isoflavone, which is found in soy beans and soy products. However other plants produce this compounds too. Red clover is another commonly found herb in herbal products.

As a side note: There are three forms of estrogen in the human body that are commonly talked about. Estradiol is the strongest. The type of estrogen used in modern-day hormone therapy is estradiol. So when you see estradiol in the rest of the article, feel free to mentally substitute “estrogen”.

Is it possible that phytoestrogens can feminize?

All things are possible.

First, let’s talk about dose. Phytoestrogens are found in very small doses in foods, or in slightly higher doses in supplements.

Medical transition requires high doses of hormones. A typical dose of estrogen today, when combined with an anti-androgen is around 4mg a day. Before antiandrogens were introduced, doses equivalent to 12mg of estradiol a day were used*. That’s a lot of hormone.

Phytoestrogen products do not come with an anti-androgen. Is it possible that they’re reaching the equivalent dose of 12mg of estradiol a day? Doses found in Canadian products ranged from 1mg to 35mg of phytoestrogens. So if phytoestrogens are equal in strength to estradiol, perhaps.

But that’s a big assumption. The body absorbs different drugs from the digestive tract in different amounts. Then that drug goes through the liver, where some portion may be activated or deactivated. And then it has to circulate around in the blood stream, find its way into the tissues of the body, and find its target. Pharmaceutical drugs have all these factors measured and calculated, so that the dose you’re given should ensure a certain dose is delivered into your tissues in the end. These herbs have not been studied in that way — so until more research is done, it’s difficult to know how much actually gets to the tissues. And it’s known that phytoestrogens bind to estrogen receptors only weakly, so they’re likely to have a weaker effect than estradiol.

In the doses that are being taken, do they have any effect?

As far as I can tell from the evidence, no. Phytoestrogens are marketed to cis women for relief from hot flashes. A study from 2003 published in JAMA found that they do not provide significant relief from hot flashes. Most of the clinical evidence that I’ve seen agrees with that study.

Phytoestrogen supplements may seem to offer an accessible, easy way to feminize. However, there’s little to no evidence behind their use. And since they’re supplements, you’re never sure of what you’ll be getting. If you want to eat foods that are high in phytoestrogen, they’re not likely to do you harm. But from what I can tell of the literature, you’re better off saving that $20 to pay for an estrogen prescription.

If you’re having difficulty finding a physician who’s will prescribe hormone therapy, I urge you to call your local transgender or LGBT center, or visit the WPATH or GLMA website for provider listings.

*: These formulations were often from conjugated estrogens, which use a slightly different dosing. Doses of conjugated estrogens ranged from 7.5 to 10mg/day, and .625mg of conjugated estrogens is roughly equivalent to 1mg of oral estradiol. My figure of 12 mg of estrogen was using the “low” dosage of 7.5mg.

Monogamy is the practice of having only one sexual, romantic, or intimate partner in one’s life. Non-monogamy, is any practice where more than two people are sexual, romantic, or intimate with each other. Though non-monogamy is an ancient practice which continues to be traditional in many societies and cultures worldwide, in the West it’s a minority behavior. Since the 1970s a particular form of non-monogamy has been emerging: polyamory (lit: “many loves”). Polyamory (“Poly”) is the practice of more than two people involved in a loving, emotionally intimate relationship where sex may or may not be involved.

Outside of that basic definition, polyamory varies widely. Polyamory can involve any number of people in any configuration. Everybody does not have to be involved with everybody else. For example, three people in a polyamorous relationship could be in a V style (i.e., persons A and B are involved, and B and C are involved, but A is not involved with C) or in a triangle relationship (i.e., persons A and B, B and C, and A and C are all in relationships). Polyamory relationships can be “open”, where new partners and relationships are welcomed, or “closed” where they are not. New relationships may be restricted to being only sexual, or not at all sexual. And polyamory relationships may be deemed more or less serious through tags like “primary” and “secondary” relationships.

But how does all this relate to health? Well, it sorta does and it sorta doesn’t.

The factor that likely pops into most minds first is sexually transmitted diseases/infections. How many times have we all been counseled to be monogamous to reduce our risk? I see that message everywhere. But it’s an incomplete message. Research is scarce on poly health, but I’m of the believe that a closed poly relationship is no more risky than a monogamous relationship. Whether a poly relationship is open or closed, safer sex techniques (including the use of barriers and regular STI testing) reduce the risk of STI spread.

More insidious are effects on mental health… but not because of polyamory alone. Polyamory itself, while taking more emotional energy than monogamy, can be incredibly fulfilling and provide abundant psychosocial support. Being poly in a non-accepting environment, however, can be very stressful. And we all know what happens when there’s additional stress. High levels of psychosocial stress are associated with: a) higher levels of depression, anxiety, self-medication via substance use, obesity, eating disorders, non-suicidal self injury, PTSD, and b) lower levels of exercise and healthy eating.

Adding an extra wrinkle: it can be very difficulty for poly-identified people to get mental health support. Finding a poly-friendly therapist (especially one covered by insurance) can be an exercise in frustration. Many mental health care professionals simply don’t understand. Others are downright discriminatory. As one poly person expressed: “I’ve had a mental health ‘professional’ refuse to even try to understand the poly nature of our family and insist that I needed to get out of the relationship before he would ‘treat’ me.” (Source)

So what’s a poly person to do? Take care of yourself. If you’re in an open relationship, be familiar with the various STDs and how they are spread, and practice good safe sex. Do what you can to take care of your mental health — exercise, eat well, get some stress relief in there too. Consider getting in touch with a local poly organization or sex-positive group. They can be invaluable for social support and finding resources when you need them.

What is Open Minded Health?

OMH is dedicated to providing information about gender and sexual minority health. Posts are a mix of the latest research, activity risk reduction tips, and the latest news.

This blog is definitely not suitable for children, and probably not work safe. It contains descriptions of sexual activities that may disturb some readers.

Also please be aware: I am not a doctor. OMH does not provide health care advice - the information here is to be used as information only. It does not substitute a visit to your health care provider. When in doubt, please ask your health care provider.

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